10-74083342-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014000.3(VCL):​c.875-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VCL
NM_014000.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.867
Variant links:
Genes affected
VCL (HGNC:12665): (vinculin) Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VCLNM_014000.3 linkc.875-24T>C intron_variant Intron 7 of 21 ENST00000211998.10 NP_054706.1 P18206-1V9HWK2B3KXA2
VCLNM_003373.4 linkc.875-24T>C intron_variant Intron 7 of 20 NP_003364.1 P18206-2A0A024QZN4B3KXA2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VCLENST00000211998.10 linkc.875-24T>C intron_variant Intron 7 of 21 1 NM_014000.3 ENSP00000211998.5 P18206-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251162
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460720
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
726702
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
15
DANN
Benign
0.79
BranchPoint Hunter
3.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1908339; hg19: chr10-75843100; API